6oio
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6oio is ON HOLD Authors: Hermans, S.J., Chung, M.C., Parker, M.W., Thomas, T., Baell, J.B. Description: Crystal structure of MYST acetyltransferase...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of MYST acetyltransferase domain in complex with inhibitor 60== | |
| + | <StructureSection load='6oio' size='340' side='right'caption='[[6oio]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6oio]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OIO FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=ML7:N-(phenylsulfonyl)[1,1-biphenyl]-3-carbohydrazide'>ML7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6oio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oio OCA], [https://pdbe.org/6oio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oio RCSB], [https://www.ebi.ac.uk/pdbsum/6oio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oio ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KAT8_HUMAN KAT8_HUMAN] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.<ref>PMID:12397079</ref> <ref>PMID:15923642</ref> <ref>PMID:20018852</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative that inhibited KAT6A with an IC50 of 0.87M. Elaboration of the structure-activity relationship (SAR) and medicinal chemistry optimization led to discovery of WM-8014 (84), a highly potent inhibitor of KAT6A (IC50 = 0.008 M). WM-8014 competes with Ac-CoA and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool. | ||
| - | + | Discovery of benzoylsulfonohydrazides as potent inhibitors of the histone acetyltransferase KAT6A.,Leaver D, Cleary B, Nguyen NT, Priebbenow DL, Lagiakos HR, Sanchez J, Xue L, Huang F, Sun Y, Mujumdar P, Mudududdla R, Varghese S, Teguh S, Charman SA, White K, Katneni K, Cuellar M, Strasser J, Dahlin J, Walters MA, Street I, Monahan B, Jarman KE, Jousset Sabroux H, Falk H, Chung M, Hermans S, Parker MW, Thomas T, Baell JB J Med Chem. 2019 Jun 29. doi: 10.1021/acs.jmedchem.9b00665. PMID:31256587<ref>PMID:31256587</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6oio" style="background-color:#fffaf0;"></div> |
| - | [[Category: Baell | + | |
| - | [[Category: Chung | + | ==See Also== |
| - | [[Category: Hermans | + | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] |
| - | [[Category: Thomas | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Baell JB]] | ||
| + | [[Category: Chung MC]] | ||
| + | [[Category: Hermans SJ]] | ||
| + | [[Category: Parker MW]] | ||
| + | [[Category: Thomas T]] | ||
Current revision
Crystal structure of MYST acetyltransferase domain in complex with inhibitor 60
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